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Studies on NG-methylarginine derivatives in myelin basic protein from developing and mutant mouse brain
1Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
The Biochemical Journal
|November 1, 1992
Summary
Myelin basic protein (MBP) methylation changes with brain development and myelin structure. Dysmyelinating mutants show altered NGNG-dimethylarginine (Me2(asym)Arg) levels, indicating myelin integrity impacts post-translational modification.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Myelin basic protein (MBP) is a key component of myelin.
- NG-methylarginine derivatives are post-translational modifications of arginine residues.
- Myelin structure and integrity are crucial for proper brain function.
Purpose of the Study:
- To investigate the levels and types of NG-methylarginine derivatives in MBP during normal myelin development and in dysmyelinating mutants.
- To determine the relationship between myelin structure and the post-translational methylation of MBP.
Main Methods:
- High-performance liquid chromatography (HPLC) with post-column o-phthaldialdehyde derivatization was used to quantify NG-methylarginine derivatives.
- Myelin basic protein (MBP) was purified from mouse brains at different developmental stages and from dysmyelinating mutants (jimpy and quaking).
- SDS-PAGE was employed to analyze MBP isoforms.
Main Results:
- All three naturally occurring NG-methylarginine derivatives (NG-monomethylarginine (MeArg), NGN'G-dimethylarginine [Me2(sym)Arg], and NGNG-dimethylarginine [Me2(asym)Arg]) were detected in MBP.
- The relative concentrations of these derivatives changed significantly with age: MeArg and Me2(sym)Arg increased, while Me2(asym)Arg decreased in normal myelin development.
- MBP from less compact myelin and from dysmyelinating mutants showed higher levels of Me2(asym)Arg compared to compact myelin and age-matched controls.
- A high-molecular-mass MBP isoform (32 kDa) was present in young and mutant brains but absent in adult brains.
Conclusions:
- Myelin structural integrity plays a critical role in regulating the extent and type of NGNG-dimethylarginine (Me2(asym)Arg) formation in MBP at the post-translational level.
- Alterations in myelin structure, as seen in dysmyelinating mutants, are associated with distinct patterns of MBP methylation.
- The presence of a high-molecular-mass MBP isoform in young and mutant brains suggests developmental or pathological changes in MBP processing or structure.